Gene therapy for glycogen storage diseases

Abstract

The present invention relates to a transcription factor EB (TFEB) protein, ortholog, recombinant or synthetic or bio technological functional derivative thereof, allelic variant thereof and fragments thereof; a chimeric molecule comprising the TFEB protein, ortholog, recombinant or synthetic or biotechnological functional derivative thereof, allelic variant thereof and fragments thereof; a polynucleotide coding for said protein or ortholog, recombinant or synthetic or biotechnological functional derivative thereof, allelic variant thereof and fragments thereof; a vector comprising said polynucleotide; a host cell genetically engineered expressing said polypeptide or a pharmaceutical composition for use in the treatment or/and prevention of a glycogen storage disease. Preferably of Pompe or Danon disease.

1 .- 31 . (canceled) 
     
     
         32 . A method of treating a glycogen storage disease comprising a step of delivering a nucleic acid encoding a transcription factor EB (TFEB) gene into a subject in need of treatment. 
     
     
         33 . (canceled) 
     
     
         34 . The method according to  claim 33  wherein the glycogen storage disease is selected from the group consisting of: GSD type Ia (Von Gierke disease), GSD type I non-a (various subtypes), GSD type II (Pompe disease), GSD type IIb (Danon disease), GSD type III (Cori's disease or Forbes' disease), GSD type IV (Andersen disease), GSD type V (McArdle disease), GSD type VI (Hers' disease), GSD type VII (Tarui's disease), GSD type IX, GSD type XI (Fanconi-Bickel syndrome), GSD type XII (Red cell aldolase deficiency), GSD type XIII and GSD type 0. 
     
     
         35 . The method according to  claim 32  wherein the glycogen storage disease is Pompe disease. 
     
     
         36 . The method according to  claim 32  wherein the glycogen storage disease is Danon disease. 
     
     
         37 . The method according to  claim 32 , wherein the nucleic acid encoding the TFEB gene is delivered to a target tissue that contains accumulated glycogen. 
     
     
         38 .- 44 . (canceled) 
     
     
         45 . The method according to  claim 32 , wherein the nucleic acid is a viral vector. 
     
     
         46 . The method according to  claim 45 , wherein the viral vector is an adeno-associated virus (AAV) vector. 
     
     
         47 . The method according to  claim 46 , wherein the AAV vector is selected from the group consisting of AAV1, AAV2, AAV5, AAV6, AAV7, AAV8, AAV9, and combinations thereof. 
     
     
         48 . The method according to  claim 47 , wherein the AAV vector is an AAV1, AAV2 or AAV9 vector. 
     
     
         49 . The method according to  claim 46 , wherein the AAV vector is a chimeric and/or pseudotyped vector. 
     
     
         50 . The method according to  claim 32 , wherein the nucleic acid further comprises a tissue specific promoter sequence that controls the expression of the TFEB gene. 
     
     
         51 . The method according to  claim 50 , wherein the tissue specific promoter sequence is a muscle specific promoter sequence, preferably it is the MCK promoter sequence consisting of SEQ ID NO: 3. 
     
     
         52 . The method according to  claim 50 , wherein the tissue specific promoter sequence is a liver specific promoter sequence, preferably it is the PEPCK promoter sequence consisting of SEQ ID NO: 4. 
     
     
         53 . The method according to  claim 32 , wherein the TFEB gene comprises a nucleotide sequence at least 60% identical to SEQ ID NO: 1. 
     
     
         54 . The method according to  claim 32 , wherein the TFEB gene comprises a nucleotide sequence at least 80% identical to SEQ ID NO: 1. 
     
     
         55 . The method according to  claim 32 , wherein the TFEB gene comprises a nucleotide sequence of SEQ ID NO: 1. 
     
     
         56 . The method according to  claim 32 , wherein the TFEB gene comprises a nucleotide sequence encoding an amino acid sequence at least 80% identical to SEQ ID NO: 2. 
     
     
         57 . The method according to  claim 32 , wherein the TFEB gene comprises a nucleotide sequence encoding an amino acid sequence at least 90% identical to SEQ ID NO: 2. 
     
     
         58 . The method according to  claim 32 , wherein the TFEB gene comprises a nucleotide sequence encoding an amino acid sequence of SEQ ID NO: 2. 
     
     
         59 .- 60 . (canceled) 
     
     
         61 . A method of treating a glycogen storage disease comprising a step of administering a nucleic acid encoding a transcription factor EB (TFEB) gene into a subject in need of treatment such that the glycogen storage in muscles and/or liver is reduced in intensity, severity, or frequency, or has delayed onset. 
     
     
         62 . (canceled) 
     
     
         63 . The method according to  claim 61  wherein the glycogen storage disease is selected from the group consisting of: GSD type Ia (Von Gierke disease), GSD type I non-a (various subtypes), GSD type II (Pompe disease), GSD type IIb (Danon disease), GSD type III (Cori's disease or Forbes' disease), GSD type IV (Andersen disease), GSD type V (McArdle disease), GSD type VI (Hers' disease), GSD type VII (Tarui's disease), GSD type IX, GSD type XI (Fanconi-Bickel syndrome), GSD type XII (Red cell aldolase deficiency), GSD type XIII and GSD type 0. 
     
     
         64 . The method according to  claim 61 , wherein the glycogen storage disease is Pompe disease. 
     
     
         65 . The method according to  claim 61 , wherein the glycogen storage disease is Danon disease. 
     
     
         66 .- 68 . (canceled) 
     
     
         69 . The method according to  claim 61 , wherein the nucleic acid is an expression vector selected in the group consisting of: viral vector, plasmids, viral particles and phages. 
     
     
         70 . The method according to  claim 69 , wherein the viral vector is selected from the group consisting of: adenoviral vectors, lentiviral vectors, retroviral vectors, adeno associated vectors (AAV) and naked plasmid DNA vectors. 
     
     
         71 . The method according to  claim 70 , wherein the AAV vector is selected from the group consisting of AAV1, AAV2, AAV5, AAV6, AAV7, AAV8, AAV9, and combinations thereof. 
     
     
         72 . The method according to  claim 71 , wherein the AAV vector is an AAV1, AAV2 or AAV9 vector.